Human immunodeficiency virus (HIV) is the etiological agent of acquired immunodeficiency syndrome (AIDS). At present there is no effective vaccine against this disease and therapeutic agents provide only limited help. The objects of this project are to characterize HIV antigens, determine the targets of humoral and cell-mediated immunity, and to use this information to develop candidate vaccines. We have constructed recombinant vaccinia viruses containing HIV genetic information. These viruses have been used as live experimental vaccines to immunize animals, to synthesize HIV proteins in tissue culture, to make targets for cytotoxic T cells, and study CD4-envelope protein interactions. Removal of cryptic poxvirus transcription termination signals that exist within the HIV-1 envelope gene was necessary for optimal expression. The envelope proteins of HIV-1, HIV-2 and SIV were shown to exist in oligomeric forms that might enhance their immunogenicity and binding to the CD4 receptor on lymphocytes. The formation of heteroligomers between HIV-1 and HIV-2 or SIV envelope proteins indicates that the domain is highly conserved. The gag-pol genes of HIV-1 were expressed and the proteins were assembled into particles that budded from the plasma membrane. Such particles represent a novel noninfectious form of HIV that might have potential as a vaccine. In addition, gag particle formation and processing have provided a useful system for testing protease inhibitors as potential therapeutic agents.